This application is organized around the framework of Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer. The organizing framework of the CR-PSOC integrates the strengths of chemistry, genetics, and physics to address chromatin dynamics in cancer. Through the use of shared model systems Center investigators will be able to integrate data from across projects to develop a new conceptual understanding of the mechanisms underlying physical rearrangement of chromatin in cancer and how that controls gene expression. The Center is composed of three interrelated project areas, each focused on different aspects of chromatin structure and function. Each project integrates emerging physical science approaches and molecular and cancer cell biology tools, as well as theory and modeling methods from the physical sciences, to achieve a quantitative and predictive understanding of the of deregulation of chromatin mechanics, epigenetic regulatory pathways, gene expression, and the nuclear environment in cancer. The Center's projects maintain a clear cancer focus rooted in understanding the molecular mechanism behind genetic alterations in chromatin regulators in cancer, particularly hematological malignancy. The scientific activities of the CR-PSOC will be supported by two shared resource cores: the Nanocytometry Core and the PDX Human Tumor Model Core. These cores will encompass unique resources that will not only benefit CR-PSOC investigators but will substantially augment the tools and approaches of investigators across the PSON. The proposed Chicago Region-Physical Science Oncology Center (CR-PSOC) brings together a unique constellation of physical science, chemical biology, and genetics expertise and couples this expertise with cutting edge analytical instrumentation, specialized sequencing technology, super high resolution imaging modalities, and novel cancer model systems. This combination of expertise and resources will enable Center investigators and members of the PSO Network to examine the structural and functional aspects of chromatin and nuclear dynamics in cancer at unprecedented depth and breadth. The CR-PSOC will provide a range of educational activities and programs designed to stimulate the interest and enhance the capabilities of the next generation of researchers working at the frontiers of physical science and oncology. Through integration of a patient advocate into Center administration with a key role in advising and supporting the translation of CR-PSOC discoveries the Center will maintain a steady focus on the importance of targeting clinical outcomes through advances in basic research.